Page 38 - 85 cell signalling pathways

Cell Signalling Biology Michael J. Berridge Module 2 Cell Signalling Pathways 2 38

Module 2: Figure cADPR action in neurons

cADPR potentiates Ca 2 + transients induced by action potentials in sympathetic neurons.
When sympathetic neurons are stimulated for 10 ms at 20 Hz, there is a distinct transient made up of Ca 2 + entering through voltage-operated
channels (VOCs) together with release of Ca 2 + from internal stores through a process of Ca 2 + -induced Ca 2 + release (CICR). The latter component
is quite variable and depends upon the sensitivity of the ryanodine receptors (RYRs). When the neurons are perfused with cyclic ADP-ribose (cADPR),
there is a large increase in the amplitude of the transient (compare responses a and b in panel A). Note how the increase developed slowly over
the recording period. There was no augmentation when the neurons were perfused with control solution (panel B). Reproduced from Neuron, Vol.
12, Hua, S.-Y., Tokimasa, T., Takasawa, S., Furuya, S., Nohmi, M., Okamoto, H. and Kuba, K., Cyclic ADP-ribose modulates Ca 2 + release channels
for activation by physiological Ca 2 + entry in bullfrog sympathetic neurons, pp. 1073–1709. Copyright (1994), with permission from Elsevier; see Hua
et al. 1994.

Module 2: Figure NAADP structure

The structure of NAADP.
The space-filling model on the right illustrates the molecular organization of the different components of NAADP. Reproduced from Curr. Biol., Vol. 13,
Lee, H.C., Ca 2 + signalling: NAADP ascends as a new messenger, pp. R186--R188. Copyright (2003), with permission from Elsevier; see Lee 2003.

NAADP control of Ca 2 + release the ryanodine receptors (RYRs), is still being defined. On
NAADP functions as a Ca 2 + -mobilizing messenger to the basis of studies carried out in sea urchin eggs, this
release Ca 2 + from an internal store (Module 2: Fig- novel store appears to reside in a lysosome-related or-
ure cADPR/NAADP function). This NAADP-sensitive ganelle. The receptors for NAADP appear to be a family
store, which is distinct from the endoplasmic retic- of two-pore channels (TPC), with TPC1 being located on
ulum/sarcoplasmic reticulum store that is regulated by the the endosomal membranes, whereas TPC2 is on lysosomal
inositol 1,4,5-trisphosphate receptors (InsP 3 Rs) and membranes.

C 2012 Portland Press Limited www.cellsignallingbiology.org